The ability of lipases and proteases to catalyze the asymmetric hydrolysis of chiral esters in water is known. However, these known methods have inherent problems including the necessity of initially converting the racemic target molecule to an ester, the insolubility of most such esters in water and the sensitivity of many compounds to water. Therefore, it has been standard practice to use organic solvents in the reaction media for the catalysis of the asymmetric hydrolysis of chiral esters in water as shown in the "Asymmetric Transformations Catalyzed by Enzymes in Organic Solvents", Acc. Chem. Res., Vol. 23, No. 4 (1990) by Alexander M. Klibanov, Massachusetts Institute of Technology; "Enzyme-Catalyzed Processes in Organic Solvents", Proc. Natl. Acad. Sci. USA, Vol. 82, pp. 3192-3196 (1985); "Preparative Production of Optically Active Esters and Alcohols using Esterase-Catalyzed Stereospecific Transesterification in Organic Media," J. Am. Chem. Soc., Vol. 106, pp. 2687-2692 (1984) and "Quantitative Analyses of Biochemical Kinetic Resolution of Emantiomers Z. Enzyme-Catalyzed Esterifications in Water-Organic Solvent Biphasic Systems," J. Am. Chem. Soc., Vol. 109 , pp. 2812-2817 (1987). Further, the acyl-enzyme intermediate in the above reaction is hydrolyzed in water, thereby regenerating the free enzyme and producing the acid. In principle, other nucleophiles may compete with water for covalent acyl-enzyme intermediate, but in aqueous solutions, hydrolysis prevails. On the other hand, if organic solvents are used as the reaction media, then the acyl-enzyme can be exposed to any nucleophile without competition from water, and therefore, hydrolysis can be replaced by a number of alternative reactions such as transesterification.
It is standard practice to prepare acetates of alcohols, diols and polyols from a variety of enzymes in organic solvents. Normally, this is done with the exclusion of water and even with the removal of water in order to drive the equilibrium to favor ester formation. This is true for both chemical and enzymatic synthesis.
It is usual in enzyme catalyzed reactions in water, when the water is in excess, that the water acts as the primary nucleophile. In this invention, even though the water is in excess, the organic diol or polyol is the primary nucleophile.
EP-A-0 280 232 (published Aug. 8, 1988) describes and claims the use of a biocatalyst derived from Corynebacterium oxydans to make a monoacetate by reacting a diol with an acetate ester. However, it simply describes a method that is carried out with a mixture of a diol, an acetate ester and a biocatalyst in an essentially all organic reaction medium.
U.S. Ser. No. 418,617 entitled "Methods for Preparing Polymerizable Monomers and Purified Transacylase from Corynebacterium Oxydans", commonly owned and assigned to Eastman Kodak Company, Rochester, N.Y., filed on Oct. 10, 1989 discloses a method for converting unsaturated esters into unsaturated polymerizable monomers using a biocatalyst derived from Corynebacterium oxydans. This method involves the step of reacting an unsaturated ester with an organic compound having a primary or secondary hydroxy group in a substantially organic environment in the presence of the noted biocatalyst.
While EP-A-0 280 232 and U.S. Ser. No. 418,617 describe important advances in the art, they fail to show how to prepare acetate esters from diols and polyols in substantially aqueous media. Because there is considerable unpredictability in the preparation of such esters, there is no certainty that the same procedures for preparing unsaturated polymerizable monomers from unsaturated esters or preparing a monoacetate from a diol can be used for preparing acetate esters from diols and polyols in substantially aqueous media.
Therefore, there continues to be a need for an economical and simple way to make acetate esters from diols and polyols by reacting a diol or polyol with an acetate ester in a substantially aqueous environment in the presence of a catalytic amount of a biocatalyst derived from Corynebacterium oxydans. For instance, there are situations whereby the alcohol substrates are not particularly soluble in organic solvents, for example, hydrophilic compounds like the sugars and pentaerythritol. Thus, it is desirable to be able to use a hydrophilic medium, i.e., aqueous medium, to run enzymatic reactions. Also, it is desirable to be able to run enzymatic esterifications of hydrophilic compounds, such as diols and polyols, e.g., sugars, in substantially aqueous media and take advantage of the chemoselectivity and steroselectivity of enzymes.
The catalytic activity of enzymes is well known. It is also well known that certain microorganisms possess enzymes which can be used as biocatalysts outside of the host to prepare useful compounds from starting materials that act as substrates for the enzymes.
In fact, EP-A-0 280 232 (published Aug. 8, 1988) discussed above discusses the catalytic activity of an enzyme produced by Corynebacterium oxydans in the process of making a monoacetate by reacting a diol with an acetate ester. Moreover, U.S. Ser. No. 229,959 (filed Aug. 9, 1988 by Green, Goodhue and Olyslager) describes and claims the use of a biocatalyst derived from Corynebacterium oxydans to make a chiral hydroxycarboxylic acid from a prochiral diol.
Biocatalysis is also described for a porcine pancreatic lipase by Zaks et al (Science, 224, pp. 1249-1251, 1984). A strain belonging to the genus Corynebacterium is known to provide certain fatty acids from an n-paraffin according to U.S. Pat. No. 3,823,070. Alkenes are oxidized by a strain of Methylococcus capsulatus according to U.S. Pat. No. 4,594,324. Other biocatalytic reactions, including the production of optically active compounds, are described for example in U.S. Pat. No. 4,008,125 and U.S. Pat. No. 4,415,657.